This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obstructive sleep apnea (OSA) is a highly prevalent disorder that may occur at any age from neonate to older adult, which is characterized by intermittent hypoxia (IH) as one of the hallmarks. It has been rising among middle-aged adults due to the increasing prevalence of obesity in the USA. Furthermore, the incidence of OSA is particularly increased during pregnancy, with potential consequences to both mother and fetus. Clinical evidence indicates that IH leads to decelerations in the rhythm of fetal heart and impose a high risk to have a baby with growth retardation. However, little is known about how oligodendrocytes (OLs) in central nervous system (CNS) respond to gestational IH exposure during sleep. In this proposal, we will focus our efforts on developmental deficits of OLs in sleep apnea-associated IH and hypothesize that OL development is susceptible to maternal sleep apnea-associated IH, and that gestational IH results in postnatal disruption of myelin sheaths and neural function in CNS, which may underlie increased vulnerability to sleep apnea or other diseases such as ADHD, Alzheimer's disease, and bipolar disorder later in life. Three aims are proposed to test these hypotheses and to characterize the molecular and cellular mechanisms underlying IH-mediated OL injury due to gestational OSA-related IH exposure: Specific aim 1: to examine OL generation, proliferation, and differentiation in mouse forebrain and spinal cord at different embryonic stages following IH exposure during gestation. Specific aim 2: to determine consequences of maternal IH exposure on myelin-forming process and myelin architecture in developing and adult mice, as well as local effects on axonal development that maybe induced or deteriorated by myelin deficit. Specific aim 3: to explore signaling molecules invovled in IH-mediated OL injury occurring in maternal sleep apnea during pregnancy. The study will be performed using wild-type/transgeneic murine models of sleep apnea. Quantitative PCR, RNA in situ hybridization, Western blotting, immunohistochemistry, and electron microscopy will be performed to study gene expression and myelin structure in OL development. Electrophysiological and behavioral assessments will be used to establish functional correlates. In addition, in ovo electroporation, EMSAs and mass spectrometric analysis will be applied for investigation of IH-elicited molecular mechanisms.